Kawashima Koichiro, Mashimo Masato, Nomura Atsuo, Fujii Takeshi
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Minato-ku, Tokyo 108-8641, Japan.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe 610-0395, Japan.
Int J Mol Sci. 2024 Apr 22;25(8):4564. doi: 10.3390/ijms25084564.
Loewi's discovery of acetylcholine (ACh) release from the frog vagus nerve and the discovery by Dale and Dudley of ACh in ox spleen led to the demonstration of chemical transmission of nerve impulses. ACh is now well-known to function as a neurotransmitter. However, advances in the techniques for ACh detection have led to its discovery in many lifeforms lacking a nervous system, including eubacteria, archaea, fungi, and plants. Notably, mRNAs encoding choline acetyltransferase and muscarinic and nicotinic ACh receptors (nAChRs) have been found in uninnervated mammalian cells, including immune cells, keratinocytes, vascular endothelial cells, cardiac myocytes, respiratory, and digestive epithelial cells. It thus appears that non-neuronal cholinergic systems are expressed in a variety of mammalian cells, and that ACh should now be recognized not only as a neurotransmitter, but also as a local regulator of non-neuronal cholinergic systems. Here, we discuss the role of non-neuronal cholinergic systems, with a focus on immune cells. A current focus of much research on non-neuronal cholinergic systems in immune cells is α7 nAChRs, as these receptors expressed on macrophages and T cells are involved in regulating inflammatory and immune responses. This makes α7 nAChRs an attractive potential therapeutic target.
洛伊发现乙酰胆碱（ACh）从青蛙迷走神经释放，戴尔和达德利发现牛脾脏中存在ACh，这些发现促成了神经冲动化学传递的证明。如今，ACh作为一种神经递质已广为人知。然而，ACh检测技术的进步使其在许多缺乏神经系统的生命形式中被发现，包括真细菌、古细菌、真菌和植物。值得注意的是，在未受神经支配的哺乳动物细胞中发现了编码胆碱乙酰转移酶以及毒蕈碱型和烟碱型ACh受体（nAChRs）的mRNA，这些细胞包括免疫细胞、角质形成细胞、血管内皮细胞、心肌细胞、呼吸道和消化上皮细胞。因此，似乎非神经元胆碱能系统在多种哺乳动物细胞中表达，并且现在应该认识到ACh不仅是一种神经递质，也是非神经元胆碱能系统的局部调节剂。在此，我们讨论非神经元胆碱能系统的作用，重点是免疫细胞。目前免疫细胞中非神经元胆碱能系统的许多研究焦点是α7 nAChRs，因为巨噬细胞和T细胞上表达的这些受体参与调节炎症和免疫反应。这使得α7 nAChRs成为一个有吸引力的潜在治疗靶点。
